B cells are lymphocytes that play a large role in the humoral immune response. They are produced in the bone marrow of most mammals, and represent 5-15% of the circulating lymphoid pool. The principal function of B cells is to make antibodies against various antigens, and are an essential component of the adaptive immune system.
Plasma B cells (also known as plasma cells) are a large mature B cells that have been exposed to antigen and produce and secrete large amounts of antibodies, which assist in the destruction of microbes by binding and facilitating targeting by phagocytes, as well as activation of the complement system. Plasma cells are sometimes referred to as antibody factories.
Several plasma cell disorders are known. Multiple myeloma is among the most prominent. Autoimmune disorders resulting from in breakdown of self-tolerance can arise from terminally differentiated plasma cells. Additional plasma cell disorders include amyloidosis, which occurs when antibodies or protein fragments accumulate in organs of the body, Waldenstrom's macroglobulinemia, a malignant blood cancer characterized by a high level of IgM antibodies in the blood and the bone marrow, plasmacytoma (which is related to multiple myeloma), POEMS syndrome (characterized by polyneuropathy, organomegaly, endocrinopathy, multiple myeloma, and skin changes), heavy-chain diseases (such as gamma heavy-chain disease (Franklin's disease), alpha heavy-chain disease (Seligmann's disease) which occurs together with a small intestinal lymphoma called immunoproliferative small intestinal disease), and Mu heavy-chain disease.
To date, there has not been an antibody therapy capable of addressing these indications. This disclosure addresses this and other needs.